目的:采用中西医结合方法治疗非酒精性脂肪肝,观察临床疗效. 方法:选择106例非酒精性脂肪肝患者,按每日就诊先后顺序随机分为中药汤剂组(C组)、中药汤剂加熊去氧胆酸组(C+U组)和护肝片组(H组).C组以清热利湿、活血解郁为治则,予自拟中...目的:采用中西医结合方法治疗非酒精性脂肪肝,观察临床疗效. 方法:选择106例非酒精性脂肪肝患者,按每日就诊先后顺序随机分为中药汤剂组(C组)、中药汤剂加熊去氧胆酸组(C+U组)和护肝片组(H组).C组以清热利湿、活血解郁为治则,予自拟中药方剂“保肝降脂汤”口服,C+U 组予同样中药方剂加熊去氧胆酸口服,H组予护肝片口服,疗程均为3 mo.分别于治疗前后检测患者的肝功能、血脂,并行肝脏的B超、CT影像学检查,分析、比较三种治疗方案的临床效果. 结果:治疗后,C+U组肝功能血清酶水平明显低于另两组(ALT:622.29±13.17nkat/L vs 728.98±15.17nkat/L和622.29±13.17 nkat/L vs 693.97±15.17 nkat/L;AST:511.77±12.00nkat/L vs 650.13±11.50 nkat/L和511.77±12.00 nkat/L vs 667.80±12.34 nkat/L;ALP:777.99±11.84 nkat/L vs 1563.31±16.00 nkat/L 和777.99±1 1.84 nkat/L vs 1605.32±20.1 nkat/L;γ-GGT: 1605.32±20.17 nkat/L vs 731.81±15.00 nkat/L和1605.32±20.17 nkat/L vs 756.32±14.17 nkat/L;P<0.011,C组与H组比较,各血清酶水平相近(ALT:728.98±15.17 nkat/L vs 693.97±15.17 nkat/L;AST:650.13±11.50 nkat/L vs 667.80±12.34 nkat/L;ALP:1563.31±16.00 nkat/L vs 1605.32±20.17; γ-GGT:731.81±15.00 nkat/L vs 756.32±14.17 nkat/L; P>0.05);C+U组、C组的总胆固醇(TC)、甘油三脂(TG)较治疗前均明显下降(C+U组治疗前后TC:7.85±0.08 mmol/L vs 2.47±0.06 mmol/L,TG:4.47±0.05 mmol/L vs 0.79±0.02 mmol/L;C组治疗前后TC:7.92±0.06 mmol/L vs 4.37±0.07 mmol/L,TG:4.34±0.05 mmol/L vs 2.46±0.05 mmol/L; P<0.01),C+U组下降较C组更为显著(2.47±0.06 mmol/L vs 4.37±0.07 mmol/L和0.79±0.02 mmol/L vs 2.46±0.05 mmol/L,P<0.01);影像学的改善为C+U组优于C组, C组优于H组,三组脂肪肝消除率分别为41.7%、27.5% 和6.67%(P<0.05);三组治疗方法的综合疗效显示,C+U 组、C组的治愈率和总有效率均高于H组,(治愈率:30.6% vs 3.3%和20.0% vs 3.3%;总有效率:94.4% vs 56.7%和82.5%vs 56.7%:P<0.01);C+U组的治愈率和总有效率高于C组,但无统计学意义. 结论:“保肝降脂汤”治疗非酒精性脂肪肝,在改善肝功能的同时,能有效地降低血脂,消除或减轻脂肪肝:该方剂与熊去氧胆酸合用,则更能显著地降低肝功能血清酶和血脂水平,肝脏的影像学改变也更加明显减轻,从而进一步提高了疗效.展开更多
Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions...Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 mg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.展开更多
目的体外HepG2细胞培养观察芒果苷(mangiferin)对多耐药相关蛋白3(multidrug resistance-associate protein 3,MRP3)和核受体孕烷X受体(pregnane X receptor,PXR)、CYP7A启动子结合因子(CYP7A promoter-binding factor,CPF)表达的影响...目的体外HepG2细胞培养观察芒果苷(mangiferin)对多耐药相关蛋白3(multidrug resistance-associate protein 3,MRP3)和核受体孕烷X受体(pregnane X receptor,PXR)、CYP7A启动子结合因子(CYP7A promoter-binding factor,CPF)表达的影响。方法用芒果苷刺激HepG2细胞72 h后,分别抽提细胞RNA、膜蛋白及核蛋白,采用半定量RT-PCR和蛋白免疫印迹检测膜转运蛋白MRP3和核受体PXR、CPF在转录与蛋白水平的表达变化。熊脱氧胆酸(ursode-oxycholic acid,UDCA)处理的HepG2细胞作为阳性对照、DMSO处理细胞为阴性对照。结果芒果苷可显著刺激HepG2细胞膜转运蛋白MRP3的mRNA(比阴性对照组高3.0倍,P<0.05)和蛋白(比阴性对照组高3.3倍,P<0.05)表达,其作用强于UDCA。芒果苷也可明显上调核受体PXR[mRNA水平增高1.7倍(P<0.05),蛋白水平增高3.7倍(P<0.01)]、CPF[mRNA水平增高2.1倍(P<0.05),蛋白水平增高4.9倍(P<0.05)]的表达。结论芒果苷刺激肝癌细胞HepG2细胞膜转运蛋白MRP3的表达上调可能与核受体PXR、CPF途径相关。展开更多
文摘目的:采用中西医结合方法治疗非酒精性脂肪肝,观察临床疗效. 方法:选择106例非酒精性脂肪肝患者,按每日就诊先后顺序随机分为中药汤剂组(C组)、中药汤剂加熊去氧胆酸组(C+U组)和护肝片组(H组).C组以清热利湿、活血解郁为治则,予自拟中药方剂“保肝降脂汤”口服,C+U 组予同样中药方剂加熊去氧胆酸口服,H组予护肝片口服,疗程均为3 mo.分别于治疗前后检测患者的肝功能、血脂,并行肝脏的B超、CT影像学检查,分析、比较三种治疗方案的临床效果. 结果:治疗后,C+U组肝功能血清酶水平明显低于另两组(ALT:622.29±13.17nkat/L vs 728.98±15.17nkat/L和622.29±13.17 nkat/L vs 693.97±15.17 nkat/L;AST:511.77±12.00nkat/L vs 650.13±11.50 nkat/L和511.77±12.00 nkat/L vs 667.80±12.34 nkat/L;ALP:777.99±11.84 nkat/L vs 1563.31±16.00 nkat/L 和777.99±1 1.84 nkat/L vs 1605.32±20.1 nkat/L;γ-GGT: 1605.32±20.17 nkat/L vs 731.81±15.00 nkat/L和1605.32±20.17 nkat/L vs 756.32±14.17 nkat/L;P<0.011,C组与H组比较,各血清酶水平相近(ALT:728.98±15.17 nkat/L vs 693.97±15.17 nkat/L;AST:650.13±11.50 nkat/L vs 667.80±12.34 nkat/L;ALP:1563.31±16.00 nkat/L vs 1605.32±20.17; γ-GGT:731.81±15.00 nkat/L vs 756.32±14.17 nkat/L; P>0.05);C+U组、C组的总胆固醇(TC)、甘油三脂(TG)较治疗前均明显下降(C+U组治疗前后TC:7.85±0.08 mmol/L vs 2.47±0.06 mmol/L,TG:4.47±0.05 mmol/L vs 0.79±0.02 mmol/L;C组治疗前后TC:7.92±0.06 mmol/L vs 4.37±0.07 mmol/L,TG:4.34±0.05 mmol/L vs 2.46±0.05 mmol/L; P<0.01),C+U组下降较C组更为显著(2.47±0.06 mmol/L vs 4.37±0.07 mmol/L和0.79±0.02 mmol/L vs 2.46±0.05 mmol/L,P<0.01);影像学的改善为C+U组优于C组, C组优于H组,三组脂肪肝消除率分别为41.7%、27.5% 和6.67%(P<0.05);三组治疗方法的综合疗效显示,C+U 组、C组的治愈率和总有效率均高于H组,(治愈率:30.6% vs 3.3%和20.0% vs 3.3%;总有效率:94.4% vs 56.7%和82.5%vs 56.7%:P<0.01);C+U组的治愈率和总有效率高于C组,但无统计学意义. 结论:“保肝降脂汤”治疗非酒精性脂肪肝,在改善肝功能的同时,能有效地降低血脂,消除或减轻脂肪肝:该方剂与熊去氧胆酸合用,则更能显著地降低肝功能血清酶和血脂水平,肝脏的影像学改变也更加明显减轻,从而进一步提高了疗效.
基金supported by grants from the National Natural Science Foundation of China(Grant NOs.:82272935,91957120 and 21974114)the Postdoctoral Fellowship Program of CPSF(Program No.:GZC20240901)+5 种基金the Xiamen Medical Industry Combined Guidance Project,China(Project No.:3502Z20244ZD2022)the Scientific Research Foundation for Advanced Talents,Xiang'an Hospital of Xiamen University,China(Grant No.:PM20180917008)the Fundamental Research Funds for the Central Universities,China(Grant No.:20720210001)Major Science and Technology Special Project of Fujian Province,China(Project No.:2022YZ036012)Joint Laboratory of School of Medicine,Xiamen University-Shanghai Jiangxia Blood Technology Co.,Ltd.,China(Grant No.:XDHT2020010C)Joint Research Center of School of Medicine,Xiamen University-Jiangsu Charity Biotech Co.,Ltd.,China(Grant No.:20233160C0002).
文摘Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 mg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
文摘目的体外HepG2细胞培养观察芒果苷(mangiferin)对多耐药相关蛋白3(multidrug resistance-associate protein 3,MRP3)和核受体孕烷X受体(pregnane X receptor,PXR)、CYP7A启动子结合因子(CYP7A promoter-binding factor,CPF)表达的影响。方法用芒果苷刺激HepG2细胞72 h后,分别抽提细胞RNA、膜蛋白及核蛋白,采用半定量RT-PCR和蛋白免疫印迹检测膜转运蛋白MRP3和核受体PXR、CPF在转录与蛋白水平的表达变化。熊脱氧胆酸(ursode-oxycholic acid,UDCA)处理的HepG2细胞作为阳性对照、DMSO处理细胞为阴性对照。结果芒果苷可显著刺激HepG2细胞膜转运蛋白MRP3的mRNA(比阴性对照组高3.0倍,P<0.05)和蛋白(比阴性对照组高3.3倍,P<0.05)表达,其作用强于UDCA。芒果苷也可明显上调核受体PXR[mRNA水平增高1.7倍(P<0.05),蛋白水平增高3.7倍(P<0.01)]、CPF[mRNA水平增高2.1倍(P<0.05),蛋白水平增高4.9倍(P<0.05)]的表达。结论芒果苷刺激肝癌细胞HepG2细胞膜转运蛋白MRP3的表达上调可能与核受体PXR、CPF途径相关。
